Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study
Artemisinin-naphthoquine (ART-NQ) is a coformulated antimalarial therapy marketed as a single-dose treatment in Papua New Guinea and other tropical countries. To build on limited knowledge of the pharmacokinetic properties of the components, especially the tetra-aminoquinoline NQ, we studied ART-NQ...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal Article |
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American Society for Microbiology
2012
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| Online Access: | http://hdl.handle.net/20.500.11937/36181 |
| _version_ | 1848754698050338816 |
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| author | Batty, Kevin Salman, Sam Moore, Brioni Benjamin, John Lee, Sook Ting Page-Sharp, Madhu Pitus, Nolene Ilett, Kenneth Mueller, Ivo Hombhanje, Francis Siba, Peter Davis, Timothy |
| author_facet | Batty, Kevin Salman, Sam Moore, Brioni Benjamin, John Lee, Sook Ting Page-Sharp, Madhu Pitus, Nolene Ilett, Kenneth Mueller, Ivo Hombhanje, Francis Siba, Peter Davis, Timothy |
| author_sort | Batty, Kevin |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | Artemisinin-naphthoquine (ART-NQ) is a coformulated antimalarial therapy marketed as a single-dose treatment in Papua New Guinea and other tropical countries. To build on limited knowledge of the pharmacokinetic properties of the components, especially the tetra-aminoquinoline NQ, we studied ART-NQ disposition in Papua New Guinea children aged 5 to 12 years with uncomplicated malaria, comparing a single dose (15 and 6 mg/kg of body weight) administered with water (group 1; n = 13), a single dose (22 and 9 mg/kg) with milk (group 2) (n = 17), and two daily doses of 22 and 9 mg/kg with water (group 3; n = 16). The plasma NQ concentration was assayed by high-performance liquid chromatography, and the plasma ART concentration was assayed using liquid chromatography-mass spectrometry. Population-based multicompartment pharmacokinetic models for NQ and ART were developed. NQ disposition was best characterized by a three-compartment model with a mean absorption half-life (t1/2) of 1.0 h and predicted median maximum plasma concentrations that ranged as high as 57 μg/liter after the second dose in group 3. The mean NQ elimination t1/2 was 22.8 days; clearance relative to bioavailability (CL/F) was 1.1 liters/h/kg; and volume at steady state relative to bioavailability (Vss/F) was 710 liters/kg. Administration of NQ with fat (8.5 g; 615 kJ) versus water was associated with 25% increased bioavailability. ART disposition was best characterized by a two-compartment model with a mean CL/F (4.1 liters/h/kg) and V/F (21 liters/kg) similar to those of previous studies. There was a 77% reduction in the bioavailability of the second ART dose (group 3). NQ has pharmacokinetic properties that confirm its potential as an artemisinin partner drug for treatment of uncomplicated pediatric malaria. |
| first_indexed | 2025-11-14T08:44:32Z |
| format | Journal Article |
| id | curtin-20.500.11937-36181 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T08:44:32Z |
| publishDate | 2012 |
| publisher | American Society for Microbiology |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-361812023-02-22T06:24:16Z Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study Batty, Kevin Salman, Sam Moore, Brioni Benjamin, John Lee, Sook Ting Page-Sharp, Madhu Pitus, Nolene Ilett, Kenneth Mueller, Ivo Hombhanje, Francis Siba, Peter Davis, Timothy Artemisinin-naphthoquine (ART-NQ) is a coformulated antimalarial therapy marketed as a single-dose treatment in Papua New Guinea and other tropical countries. To build on limited knowledge of the pharmacokinetic properties of the components, especially the tetra-aminoquinoline NQ, we studied ART-NQ disposition in Papua New Guinea children aged 5 to 12 years with uncomplicated malaria, comparing a single dose (15 and 6 mg/kg of body weight) administered with water (group 1; n = 13), a single dose (22 and 9 mg/kg) with milk (group 2) (n = 17), and two daily doses of 22 and 9 mg/kg with water (group 3; n = 16). The plasma NQ concentration was assayed by high-performance liquid chromatography, and the plasma ART concentration was assayed using liquid chromatography-mass spectrometry. Population-based multicompartment pharmacokinetic models for NQ and ART were developed. NQ disposition was best characterized by a three-compartment model with a mean absorption half-life (t1/2) of 1.0 h and predicted median maximum plasma concentrations that ranged as high as 57 μg/liter after the second dose in group 3. The mean NQ elimination t1/2 was 22.8 days; clearance relative to bioavailability (CL/F) was 1.1 liters/h/kg; and volume at steady state relative to bioavailability (Vss/F) was 710 liters/kg. Administration of NQ with fat (8.5 g; 615 kJ) versus water was associated with 25% increased bioavailability. ART disposition was best characterized by a two-compartment model with a mean CL/F (4.1 liters/h/kg) and V/F (21 liters/kg) similar to those of previous studies. There was a 77% reduction in the bioavailability of the second ART dose (group 3). NQ has pharmacokinetic properties that confirm its potential as an artemisinin partner drug for treatment of uncomplicated pediatric malaria. 2012 Journal Article http://hdl.handle.net/20.500.11937/36181 10.1128/AAC.06250-11 American Society for Microbiology unknown |
| spellingShingle | Batty, Kevin Salman, Sam Moore, Brioni Benjamin, John Lee, Sook Ting Page-Sharp, Madhu Pitus, Nolene Ilett, Kenneth Mueller, Ivo Hombhanje, Francis Siba, Peter Davis, Timothy Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study |
| title | Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study |
| title_full | Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study |
| title_fullStr | Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study |
| title_full_unstemmed | Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study |
| title_short | Artemisinin-Naphthoquine Combination Therapy for Uncomplicated Pediatric Malaria: a Pharmacokinetic Study |
| title_sort | artemisinin-naphthoquine combination therapy for uncomplicated pediatric malaria: a pharmacokinetic study |
| url | http://hdl.handle.net/20.500.11937/36181 |